Paralytic lagophthalmos and ectropion by leprosy are serious complications of facial paralysis, which may lead to exposure keratitis, corneal ulceration, and further lead to blindness. In 1995 and 1997, we reported in this journal on the surgical treatment of 38 patients and 98 patients suffering with paralytic lagophthalmos and ectropion. In the first report of 1995, for lid closing I(Ahn) performed the method of traditional surgery such as temporal muscle transfer, medial and lateral canthoplasty as well as gold implant. In the 2nd report of 1997, we(Ahn and Park) presented the results of our combination treatment that changed the design and weight of the gold plate inserted in upper lid, and the medial canthoplasty and horizontal shortening in lower lid. Combination treatment provided for near normal eye closure and aesthetically pleasing appearance without the drawbacks associated with other methods such as eye clinching in concert with mouth closure, donor site deformities resulting from temporalis muscle transfer, and over exposure of carbuncle due to stretching effects of lateral canthoplasty. We have now found that raising the level of the lower lid margin to the sclera is important in concealing the scleral show due to drooping of the lower lid. We grafted conchal cartilage in a 5 x 35 mm sized band, which was fixed at the medial and lateral canthal area in 57 patients during the recent 3 years. We also added the ancillary procedure of the horizontal shortening in cases of highly atonic lower lid. We have noted that gold implantation in the upper eyelid and cartilage graft in the lower eyelid, with optional horizontal shortening, successfully corrected the lagophthalmos and ectropion due to facial nerve palsy.
Blindness ; Carbuncle ; Cartilage* ; Congenital Abnormalities ; Corneal Ulcer ; Ectropion* ; Eyelids ; Facial Nerve ; Facial Paralysis ; Humans ; Keratitis ; Leprosy ; Mouth ; Paralysis ; Sclera ; Temporal Muscle ; Tissue Donors ; Transplants

Recent advances in artificial intelligence (AI) have provided novel tools for rapid and precise pathologic diagnosis. The introduction of digital pathology has enabled the acquisition of scanned slide images that are essential for the application of AI. The application of AI for improved pathologic diagnosis includes the error-free detection of potentially negligible lesions, such as a minute focus of metastatic tumor cells in lymph nodes, the accurate diagnosis of potentially controversial histologic findings, such as very well-differentiated carcinomas mimicking normal epithelial tissues, and the pathological subtyping of the cancers. Additionally, the utilization of AI algorithms enables the precise decision of the score of immunohistochemical markers for targeted therapies, such as human epidermal growth factor receptor 2 and programmed death-ligand 1. Studies have revealed that AI assistance can reduce the discordance of interpretation between pathologists and more accurately predict clinical outcomes. Several approaches have been employed to develop novel biomarkers from histologic images using AI. Moreover, AI-assisted analysis of the cancer microenvironment showed that the distribution of tumor-infiltrating lymphocytes was related to the response to the immune checkpoint inhibitor therapy, emphasizing its value as a biomarker. As numerous studies have demonstrated the significance of AI-assisted interpretation and biomarker development, the AI-based approach will advance diagnostic pathology.

Purpose: The purpose of this study was to analyze the transcriptomic changes in the striatum of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and uncover its association with the methyl-CpG binding protein 2 (MeCP2) mediated-changes in striatal epigenetic signature during Alzheimer disease (AD) pathological progression. Methods: To observe transcriptomic alterations in the striatum before the onset of cognitive impairment in APP/PS1 mice, quantitative 3’mRNA sequencing was performed with RNA extracted from the striatum of 6-month-old and 12-month-old wildtype and APP/PS1 mice. In addition, chromatin immunoprecipitation sequencing was conducted with the DNA from wildtype and APP/PS1 mice of the same age as aforementioned. For transcriptomic analysis, comparison terms were constructed based on aging and transgene expression—normal-aging (12-month-old wildtype/6-month-old wildtype), early-AD (6-month-old APP/PS1/6-month-old wildtype), and late-AD (12-month-old APP/PS1/6-month-old wildtype). To compare the changes in biological pathways and networks, we analyzed gene lists from each comparison term via bioinformatics tools including DAVID (Database for Annotation, Visualization, and Integrated Discovery), STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), and SynGO (Synaptic Gene Ontologies). Furthermore, to assume the effect MeCP2 in AD pathological conditions may have on the transcriptome regulation, analysis of the common genes from Quant-Seq and MeCP2-ChIP-Seq was performed. Results: Enriched pathways including immune system and inflammatory response were confirmed in normal- aging and lateAD, respectively. In particular, enriched pathways of gene expression regulation, transcriptional regulation, and protein catabolic pathways were found to be significantly altered in early-AD. MeCP2-bound genes that were significantly altered in the transcriptome were suggested to be target genes that have a role in the striatum of the early-stage AD model. Conclusions This study confirmed that the alteration of the striatal transcriptomic profile in APP/PS1 mice was involved with several biological pathways. Additionally, comparative analysis of the transcriptomic changes and the MeCP2 bound regions found that a group of differentially expressed genes may be regulated under the epigenetic control of MeCP2.

Since the early 2000s, there has been a continued interest in lie detection using functional magnetic resonance imaging (fMRI) in neuroscience and forensic sciences, as well as in newly emerging fields including neuroethics and neurolaw. Related fMRI studies have revealed converging evidence that brain regions including the prefrontal cortex, anterior cingulate cortex, parietal cortex, and anterior insula are associated with deceptive behavior. However, fMRI-based lie detection has thus far not been generally accepted as evidence in court, as methodological shortcomings, generalizability issues, and ethical and legal concerns are yet to be resolved. In the present review, we aim to illustrate these achievements and limitations of fMRI-based lie detection.
Brain ; Deception* ; Forensic Sciences ; Gyrus Cinguli ; Lie Detection* ; Magnetic Resonance Imaging* ; Neurosciences* ; Prefrontal Cortex ; Rabeprazole

Chimeric antigen receptor (CAR) T cells, which express a synthetic receptor engineered to target specific antigens, have demonstrated remarkable potential to treat haematological malignancies. However, their transition beyond haematological malignancy has so far been unsatisfactory. Here, we discuss recent challenges and improvements for CAR T cell therapy against solid tumors: Antigen heterogeneity which provides an effective escape mechanism against conventional mono-antigen-specific CAR T cells; and the immunosuppressive tumor microenvironment which provides physical and molecular barriers that respectively prevent T cell infiltration and drive T cell dysfunction and hypoproliferation. Further, we discuss the application of CAR T cells in infectious disease and autoimmunity.

Purpose: In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating a functional interplay between basal ganglia structures and hippocampal regions. Zinc finger and BTB domain-containing protein 16 (ZBTB16) is a transcription factor that controls the expression of downstream genes and the involvement of ZBTB16 in the striatum undergoing pathological aging in AD and the resulting behavioral phenotypes has not yet been explored. Methods: To study molecular alterations in AD pathogenesis, we analyzed the brain from amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice. The molecular changes in the striatal region of the brain were analyzed via the immunoblotting, and the quantitative RNA sequencing. The cognitive impairments of APP/PS1 mice were assessed via 3 behavioral tests: 3-chamber test, Y-maze test, and noble object recognition test. And multielectrode array experiments for the analysis of the neuronal activity of the striatum in APP/PS1 mice was performed. Results: We found that the alteration in ZBTB16 levels that occurred in the early ages of the pathologically aging striatum coalesces with the disruption of transcriptional dysregulation while causing social memory deficits, anxiety-like behavior. The early ZBTB16 knockdown treatment in the striatum of APP/PS1 mice rescued cognition that continued into later age. Conclusions This study demonstrates that perturbation of transcriptional regulation of ZBTB16 during pathological aging may influence cognitive impairments and reveals a potent approach to targeting the transcriptional regulation of the striatum for the treatment of AD.

PURPOSE: To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. RESULTS: At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ≥2 toxicities were observed during or after radiotherapy. CONCLUSION: Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results.
Carcinoma, Renal Cell* ; Follow-Up Studies ; Humans ; Incidence ; Molecular Targeted Therapy* ; Multivariate Analysis ; Neoplasm Metastasis* ; Radiotherapy ; Retrospective Studies ; Treatment Outcome*

Although Toxocara canis is known to cross the blood-brain barrier, central nervous system involvement is uncommon. Clinical manifestations vary and include cerebral infarction, meningoencephalitis, myelitis, vasculitis or seizure. However cerebral infarction and meningoencephalitis rarely occur simultaneously. We report a case of multiple cerebral infarction combined with eosinophilic meningoencephalitis in a patient with neurotoxocariasis. After control of increased intracranial pressure and treatment with albendazole and steroid, the patient’s clinical symptoms improved markedly.

Acute puerperal uterine inversion is a rare postpartum obstetric complication; however, without rapid diagnosis and appropriate management, it is life-threatening. Substantial bleeding hinders the verification of a partially inverted uterus, possibly delaying the treatment. Herein, we present the report of a 32-year-old female presenting with massive postpartum bleeding managed by uterine artery embolization. The peculiar course of the uterine artery bowing inferiorly along the inverted fundus during embolization could uncover the uterine inversion, which was not diagnosed by physical examination and CT. In conclusion, uterine artery embolization is not only an effective therapeutic strategy for postpartum hemorrhage but also a valuable tool for diagnosing uterine inversion.